1. Field of the Invention
The present invention relates to an agent for reducing body fat, comprising a dioxabicyclo[3.3.0]octane derivative as an active ingredient, and use of the same in the fields of food and drink products and feeds.
2. Background Art
In recent years, patients suffering from obesity have been increased also in Japan, and this is becoming a serious social problem. The Ministry of Health and Welfare has published, in November of last year, the outline of the results of the National Nutrition Survey in 1997, and has pointed out that, as compared with 10 years ago and 20 years ago, the proportion of obesity and overweight in men tends to increase, and one out of four men in twenties and one out of three men in thirties suffer from obesity or overweight. Possible factors in this include increased ingestion (hyperphagia), reduced excercise (lack of excercise), and a fluctuation in generation of body heat. Obesity causes accumulation of a large amount of body fat. This is causative of arteriosclerosis, hypertension, diabetes, and cardiac diseases, and, in some cases, leads to complications, such as angiopathy, neuropathy, and aphylaxis.
In a society these days in which health is a matter of interest, attention is drawn to the content of fat in foods, and meat having low saturated fatty acid content is preferred. Further, a great concern is shown for diet, fitness and the like for regulating body fat, particularly subcutaneous fat, visceral fat or the like, of humans.
Under these circumferences, there is a great social demand for body fat reducing agents which have excellent function and effect and are safe.
Dioxabicyclo[3.3.0]octane derivatives, particularly sesamin, are reported in an article entitled xe2x80x9cSesamin: A multifunctional Gift From Nature,xe2x80x9d M. Sugano and K. Akimoto, xe2x80x9cJournal of Chinese Nutrition Society,xe2x80x9d 18, 1-11 (1993). This article describes, as possible advantages of sesamin, that sesamin interferes xcex4-5-desaturase, an enzyme capable of unsaturating a reaction by which dihomo-xcex3-linolenic acid is converted to arachidonic acid. This article further cites references discussing other possible effects of sesamin (activity to lower blood cholesterol, enhancement in detoxification of chemical materials and alcohols in the liver, protection against chemically induced breast cancer, and in vivo antioxiizing activity).
So far as the present inventors know, however, up to now, there have been no report such that dioxabicyclo[3.3.0]octane derivatives have activity to reduce body fat.
Accordingly, it is an object of the present invention to provide a novel agent for reducing body fat, which is highly stable and causes no significant side effect, and food and drink products and feeds containing the same.
The present inventors have repeated extensive and intensive studies using fat around kidney and fat around epididymis as an index of a reduction in body fat and, as a result, have found that dioxabicyclo[3.3.0]octane derivatives, which have been extracted or isolated from pepper seed, sesame meal, sesame oil or the like, or alternatively have been chemically synthesized, have activity to reduce body fat. This has led to the completion of the present invention.
Thus, the present invention provides an agent for reducing body fat, comprising a dioxabicyclo[3.3.0]octane derivative as an active ingredient, and a food or drink product and a feed having activity to reduce body fat, comprising said derivative.
The dioxabicyclo[3.3.0]octane derivative to be used in the present invention is represented by formula (I): 
wherein R1 to R6 each independently represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, provided that R1 and R2 and/or R4 and R5 may combine together to form a methylene or ethylene group; and n, m, and 1 are each 0 or 1.
Specific examples of dioxabicyclo[3.3.0]octane derivatives include sesamin, sesaminol, episesamin, episesaminol, sesamolin, 2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-hydroxyphenyl)-3,7-dioxabicyclo[3.3.0]-octane, 2,6-bis-(3-methoxy-4-hydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, 2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-hydroxyphenoxy)-3,7-dioxabicyclo[3.3.0]-octane, and other compounds. Among them, sesamin, episesamin, or a mixture of sesamin with episesamin is preferred.
These compounds may also be in the form of glycoside, and optically active substances are also embraced in the present invention.
According to the present invention, the dioxabicyclo[3.3.0]octane derivatives (hereinafter referred to as xe2x80x9cderivative of the present inventionxe2x80x9d) may be used either solely or in a combination of two or more. The derivative of the present invention is not limited to a highly purified product, and may also be an extract composed mainly of one or a plurality of dioxabicyclo[3.3.0]octane derivatives described above (hereinafter referred to as the xe2x80x9cextract composed mainly of the derivative of the present inventionxe2x80x9d). The extract composed mainly of the derivative of the present invention may be extracted from a naturally occurring product containing the derivative of the present invention by a conventional method. Naturally occurring products containing the derivative of the present invention include sesame oil, sesame meal, by-products obtained in the production process of sesame oil, sesame seed, acanthoponacis cortex, paulownia tree, bark of hakuka, long pepper, and asiasarum root. The content of the derivative of the present invention in the extract composed mainly of the derivative of the present invention is generally not less than 0.1% by weight, preferably not less than 1.0% by weight, more preferably not less than 5.0% by weight. In particular, desirably, the total content of sesamin and episesamin is not less than 0.05% by weight, preferably not less than 0.5% by weight, more preferably not less than 2.0% by weight.
When the derivative of the present invention is used as pharmaceutical preparations, the administration form may be any dosage form so far as oral administration can be conveniently carried out. The pharmaceutical preparations may be used either solely or in a combination of two or more, depending upon symptoms of patients.
These various preparations may be formulated by adding, to the basis, known adjuvants commonly used in the field of pharmaceutical preparations, such as fillers, binders, antiseptics, stabilizers, disintegrators, lubricants, and corrigents, depending upon purposes, according to a conventional method. If necessary, tonicity agents, stabilizers, antiseptics, and soothing agents may be added thereto.
External preparations, such as ointments and creams, may be formulated by a conventional method using as a base petrolatums, paraffins, fats and oils, lanolins, macrogols or the like. The dose may vary depending upon the purpose of administration and conditions of a subject, to which the preparation is to be administered, for example, sex, age, and weight. In general, however, in the case of oral administration to an adult, the dose may be properly regulated so that the total amount of the derivative of the present invention is 1 mg to 10 g, preferably 1 mg to 2 g, more preferably 1 mg to 200 mg, per day. On the other hand, in the case of parenteral administration, the dose may be properly regulated so that the total amount of the derivative of the present invention is 0.1 mg to 1 g, preferably 0.1 mg to 200 mg, more preferably 0.1 mg to 100 mg, per day.
The derivative of the present invention, when administered together with a conjugated linoleic acid, can enhance the effect of reducing body fat according to the present invention. When the derivative of the present invention is used in combination with the conjugated linoleic acid, the mixing ratio between the derivative of the present invention and the conjugated linoleic acid may be properly regulated in the range of 0.01 to 100 parts by weight, preferably 0.1 to 40 parts by weight, of the conjugated linoleic acid, based on one part by weight of the derivative of the present invention.
When the derivative of the present invention or an extract composed mainly of this derivative is used as food or drink products or feeds (including pet foods), this may be used in the same form as the above pharmaceutical preparations, or alternatively may be in the form of solid or liquid foods or luxury foods, for example, agricultural foods, such as breads, noodles, boiled rice, confectionery (biscuits, cakes, candy or sweets, chocolates, Japanese-style confectionery), bean curds, and processed products thereof, fermented foods, such as refined sake, medicated wine, sweet sake, vinegar, soy sauce, and miso (fermented soybean paste), fat-and-oil foods, such as dressing, mayonnaise, margarin, shortenning, and edible fats and oils, livestock products, such as yoghurt, ham, bacon, and sousage, sea foods, such as boiled fish paste, fries of mixed ingredients, and fish cakes, and other processed products, such as fruit juice, refreshing drinks, sport drinks (isotonic drinks), alcoholic drinks, and teas.
When the derivative of the present invention or an extract composed mainly of this derivative is used as health foods or functional foods, this may be used in the form of pharmaceutical preparations or foods and drinks, or alternatively may be used, for example, in the form of processed forms, such as spontaneously fluidized foods, semi-digestion nutritional foods and ingredient nourishing foods with proteins (although lactoproteins, soybean proteins, egg albumin and other proteins, which have good amino acid balance and high nutritive value, are most widely used as a protein source, for example, degradation products thereof, oligopeptides of egg white, hydrolysates of soybean and the like and, in addition, a mixture of amino acids per se may also be used), saccharides, fat, trace elements, vitamins, emulsifiers, or spices being added thereto, and health drinks.
The food or drink product or feed according to the present invention may be produced by adding a predetermined amount of the derivative of the present invention or an extract composed mainly of the derivative to a food material substantially free from the derivative of the present invention and processing the mixture by a conventional method. The mixing ratio of the derivative or the extract may vary depending upon the dosage form and the form and properties of foods, and is not particularly limited. In general, however, the mixing ratio is preferably 0.001 to 50%.
Preferably, the amount of the food or drink product according to the present invention to be orally ingested is approximately such that the total amount of the derivative of the present invention is 1 mg to 10 g, preferably 1 mg to 2 g, more preferably 1 mg to 200 mg, per day per adult. Further, the food or drink product according to the present invention, when mixed with conjugated linoleic acid, can enhance the effect of reducing body fat attained by the derivative of the present invention. In this case, the mixing ratio between the derivative of the present invention and the conjugated linoleic acid may be in the range of 0.01 to 100 parts by weight, preferably 0.1 to 40 parts by weight, of the conjugated linoleic acid, based on one part by weight of the derivative of the present invention.
The following experimental examples demonstrate that dioxabicyclo[3.3.0]octane derivatives have activity to reduce body fat.
Conjugated linoleic acid and sesamin used in the following examples were prepared by the following method.
[Preparation of Conjugated Linoleic Acid (CLA)]
50 g of potassium hydroxide was dissolved in 150 g of propylene glycol. Nitrogen was then bubbled through the solution for 20 min, and the temperature was raised to 170xc2x0 C. After raising the temperature, 100 g of a safflower oil was added to the solution, and a reaction was allowed to proceed at 170xc2x0 C. for one hr under a nitrogen stream. After the completion of the reaction, the reaction solution was cooled to room temperature, and then neutralized with hydrochloric acid, followed by stirring for 15 min. Subsequently, the reaction solution was adjusted to pH 3, and distilled water was added thereto. The mixture was stirred for 5 min. Next, extraction with hexane was carried out three times. The hexane solution was washed with a 5% NaCl solution and distilled water, and then dehydrated and filtered. After the filtration, hexane was removed by distillation to give a conjugated linoleic acid-containing fatty acid.
[Preparation of Sesamin]
400 parts of an 80% aqueous ethanol solution as a solvent was added to 100 parts of scum as a by-product obtained in the production process of a sesame oil (a distillate obtained in the step of deodorization). The mixture was heated under reflux with stirring for one hr, cooled to 20xc2x0 C., and then allowed to stand at that temperature overnight to prepare a mixed solution. The mixed solution consisted of two separated phases, a solvent-soluble fraction and a solvent-insoluble fraction. The solvent-soluble fraction was separated from the mixed solution by stratification separation. 24.7 parts of 48% potassium hydroxide was added to and mixed with the separated solvent-soluble fraction. The mixed solution was allowed to stand at 10xc2x0 C. overnight to precipitate sesamins. The precipitated sesamins were separated by suction filtration, washed with 100 parts of water, and dried at 80xc2x0 C. for 3 hr. Thus, a brown solid was obtained. The brown solid was analyzed and found to be a 1:1 mixture (purity 99.5%) of sesamin and episesamin.